Christos B. Moschos

Cardiovascular effects of long-term cigarette smoking and nicotine administration☆

The nature of the cardiovascular risk in cigarette smokers has not been characterized. To compare the relative effects of long-term smoking and nicotine administration on the cardiovascular system, 18 month old beagle littermates were prepared with a permanent tracheostomy. They were classified into three groups: I, seven control dogs; II, nine dogs that smoked seven cigarettes/day; and III, eight dogs that received an equivalent amount of nicotine. After a period of up to 22 months, the animals were catheterized under anesthesia for assessment of left ventricular function and volumes by indicator-dilution technique. Heart rate, stroke volume, left ventricular end-diastolic pressure and volume and intraventricular conduction times did not differ significantly in the three groups. Left ventricular ejection fraction was 44 +/- 3 percent (mean +/- standard error of the mean) in the control group, 35 +/- 3 percent in the dogs that smoked cigarettes (P less than 0.05) and 27 +/- 3 percent in those given nicotine (P less than 0.01) despite similar values for end-diastolic variables in the three groups. The first derivative of left ventricular pressure (dP/dt) normalized for pre- and afterload was 2.4 +/- 0.2 cm/sec -1 in the control group, 1.41 +/- 0.12 in the cigarette-smoking group (P less than 0.005) and 1.34 +/-0.08 in the nicotine group (P less than 0.01). Although mean aortic pressure was significantly elevated in both the smoking (127 +/- mm Hg) and nicotine (127 +/- 10 mm Hg) groups, there was no significant correlation with the contractility indexes. Reduction of afterload to normal levels did not affect the abnormal ventricular performance. Hypertrophy, inflammation and abnormalities of cell ultrastructures were not present, and myocardial lipid and cation composition were normal. Since interstitial fibrosis was evident in both experimental groups, an alteration of elastic elements may be operative. These cardiovascular abnormalities appear to be predominantly dependent on the nicotine of cigarettes.

Effect of aspirin upon experimental coronary and non-coronary thrombosis and arrhythmia.

Abstract The effect of aspirin upon platelet function led to speculation on the potential effects of salicylates upon arterial thrombogenesis, in which platelets play a primary role. Aspirin was given by mouth or intravenously before attempting induction of coronary or femoral artery thrombosis in dogs by means of a catheter electrode. The incidence of thrombus formation in all animals receiving aspirin was comparable to that of the control groups. Although in several animals of coronary thrombus group receiving aspirin, the thrombus was smaller than in the controls, this was not statistically significant. An unexpected finding was the distinct decrease in incidence of arrhythmias and ventricular fibrillation in the coronary thrombus group treated with aspirin. The reason for the differences is not clear at this time.

Depression of Cardiac Function and Altered Myocardial Metabolism After Ethanol.

Excerpt In view of the ill-defined status of cardiac involvement in chronic alcoholism, a study of the acute effects of ethanol on myocardial metabolism and function has been undertaken in animals ...

Chronic smoking in an animal model: Effects on clotting and fibrinolysis☆

The effects of chronic smoking upon fibrinogen turnover and other clotting parameters, were studied prospectively in an animal model maintained on a chronic program for a period of 18 months. The animal received the equivalent on a weight basis of 11/2 packs of cigarettes daily, smoked by a human subject with the weight of 70 kg. The obtained results suggested significant enhancement of the coagulation mechanism in the smoking animals developing over the period of observation particularly when combined with high lipid diet.

Chronic use of aspirin versus indomethacin during non-thrombotic myocardial ischemia: effects on survival.

In view of the reported disparity of the effects upon ischemic myocardium of aspirin and indomethacin, both affecting platelet function and prostaglandin metabolism, we utilized a closedchest canine model to study the effects of chronic treatment with these agents upon arrhythmias, during non-thrombotic coronary occlusion. Group A (N = 20) and Group B (N = 20) were pretreated for seven consecutive days with aspirin 600 mg./day and with indomethacin 25 mg./day, respectively. A group of 36 non-treated animals served as controls. Determination of hemodynamics revealed no significant differences in left ventricular function among the various groups, although blood pressure levels were consistently higher in Group B. Precordial ECG mapping showed lower magnitude of myocardial ischemia in the aspirin group. Changes in water and cation composition of the ischemic tissue after four hours of coronary occlusion were also significantly lower in the aspirin group, suggesting that more extensive tissue swelling in the indomethacin group might have contributed by means of more intensive ischemia, to a higher incidence of ventricular fibrillation. Consistently higher blood pressure levels requiring increased mechanical demands on the myocardium would enhance the negative results observed in the indomethacin group. Mortality rate was 5% for the aspirin group versus 40% and 39% for the indomethacin and the non-treated groups, respectively (P < 0.015). The failure to observe significant platelet accumulation by radioactivity counts in either treated or non-treated animals using 51Cr and 111In-labelled platelet, indicated that microcirculatory thrombosis was not a feature in this model. It is not clear to what extent the reported diverse, mostly inhibitory, effects upon the various enzyme systems and lysosomal membrane ascribed to antiinflammatory agents, are applicable more for indomethacin per se or for the therapeutic schedule used in this study in order to explain its different effect upon ischemic myocardium.

Myocardial effects of long-term cigarette smoking: Relative roles of carbon monoxide and nicotine

Abstract In a prior study of an animal model exposed to long-term cigarette smoking, left ventricular performance was observed to decline in association with morphologic evidence of collagen accumulation. Because controversy has existed as to whether nicotine or carbon monoxide is the major pathogenetic agent in cigarette smoking, 18 young adult male beagles with chronic tracheostomy were placed in three groups of six dogs each: Group 1 served as a control group; group 2 received seven cigarettes of low nicotine content (0.2 mg/cigarette), which effected a peak carboxyhemoglobin level approximating 5/100 ml, similar to that of regular cigarettes; and group 3 received nicotine twice daily intramuscularly in an amount equivalent to seven cigarettes/day. In the intact anesthetized state, heart rate, left ventricular end-diastolic pressure and volume (indicator dilution) did not differ among the three groups. To assess relative myocardial wall stiffness, saline solution was infused into the left ventricular chamber. A significantly higher end-diastolic pressure and tension were elicited in group 3, suggesting a decrease in left ventricular compliance. No such change was observed in either group 1 or 2. Only long-term nicotine use was associated with increased hydroxyproline content in the left ventricular myocardium, suggesting a basis for enhanced stiffness. An index of left ventricular contractility was derived from the peak rate of rise of left ventricular pressure ( dP dt ), normalized for preload and afterload. Groups 1 and 2 showed no difference in this index (2.18 ± 0.3 versus 2.15 ± 0.18 muscle lengths/s per cm) at similar levels of aortic pressure, but the index was significantly lower (1.28 ± 0.12, p

Traumatic rupture of the thoracic aorta simulating coarctation

Abstract A case of rupture of the thoracic aorta following trauma is presented, and the mechanisms resulting in such lesions are reviewed. It is stressed that such lesions may occur in the absence of any obvious trauma to the chest. The unusual feature of localized intimal dissection resulting in partial obstruction of the aorta and development of the clinical picture of coarctation is described.